Public Release: 

Quantifying physical changes in red blood cells as they mature in the bloodstream


During their approximately 100-day lifespan in the bloodstream, red blood cells lose membrane surface area, volume, and hemoglobin content. A study publishing this week in PLOS Computational Biology finds that of these three changes, only the observed surface-area loss can be explained by RBCs shedding small hemoglobin-containing vesicles budding off their cells' membrane.

Red blood cell concentration, mean volume, and hemoglobin content are routinely measured in the complete blood count, a fundamental clinical test essential to the screening, diagnosis, and management of most diseases. Variation in mean volume and hemoglobin content is associated with many important clinical conditions, but we do not understand the mechanisms controlling these physical characteristics of red blood cells. Vesicle shedding had been thought to be the most important, but researchers Roy Malka and John Higgins from Massachusetts General Hospital/Harvard Medical School, with colleagues from Massachusetts Institute of Technology, show that a dominant role for vesicle shedding would violate empirical geometric and biophysical constraints. An additional unknown process must be primarily responsible. The study shows that this important process must be coupled to changes in red blood cell surface area and quantifies the magnitude of its effects.

The study required a multidisciplinary team with expertise in applied mathematics, engineering and medicine. The work combines mathematical modeling of the mechanism that changes the physical properties of the cells, clinical measurements of both cellular volume and hemoglobin content, and data from a new system for characterizing the non-water cellular mass of individual cells.

Maturation of red blood cells in the circulation, the subject of this study, is one of the three major components controlling the population of red blood cells, the other two being their production by the bone marrow and clearance from the circulation.

The researchers conclude that the quantitative characterization of red blood cell loss processes will help "focus future investigation of the molecular mechanisms of red blood cell maturation", the characterization of which "may help in the early detection of clinical conditions where the maturation pattern is altered".


All works published in PLOS Computational Biology are Open Access, which means that all content is immediately and freely available. Use this URL in your coverage to provide readers access to the paper upon publication:


Roy Malka
Harvard Medical School
Systems Biology
Center for Systems Biology
Massachusetts General Hospital
Boston, MA 02114
Phone: 8572949492

Citation: Malka R, Delgado FF, Manalis SR, Higgins JM (2014) In Vivo Volume and Hemoglobin Dynamics of Human Red Blood Cells. PLoS Comput Biol 10(10):e1003839. doi:10.1371/journal.pcbi.1003839

Funding: This work was funded by the Institute for Collaborative Biotechnologies Contract W911NF-09-D-0001 from the US Army Research Office (SRM). NIH Director's New Innovator Award and NIH grant 1DP2DK098087 (JMH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

About PLOS Computational Biology

PLOS Computational Biology features works of exceptional significance that further our understanding of living systems at all scales through the application of computational methods. All works published in PLOS Computational Biology are Open Access. All content is immediately available and subject only to the condition that the original authorship and source are properly attributed. Copyright is retained. For more information follow @PLOSCompBiol on Twitter or contact

About PLOS

PLOS is a nonprofit publisher and advocacy organization founded to accelerate progress in science and medicine by leading a transformation in research communication. For more information, visit

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.